The urinary proteome in diabetes and diabetes-associated complications: New ways to assess disease progression and evaluate therapy

Diabetes represents one of the main chronic diseases worldwide. Diabetes and its associated complications may be detectable even at early stages in the urinary proteome. In this article we review the current literature on urinary proteomics applied to the study of diabetes and diabetic complications. Further, we present recent data that strongly indicate urinary proteome analysis may be a valuable tool in detecting diabetes-associated pathophysiological changes at an early stage, and also may enable assessment of disease progression and efficacy of therapy. Current data indicate that collagen-derived peptides represent one of the main peptidic components in urine, which are consistently found at reduced levels in diabetes. It is tempting to speculate that this decrease in urinary collagen-derived peptides is related to an increase in extracellular matrix deposition which is a major complication in diabetes. Therefore, urinary proteome analysis might enable noninvasive assessment of this process at an early stage via determination of specific collagen fragments. This may open an avenue towards targeted therapeutic intervention.     

Identification of a putative binding site for 5-alkyl-benzothiadiazides in the AMPA receptor dimer interface

Crystal structures of three different allosteric modulators co-crystallized with the iGluR2 ligand-binding domain are currently available. The modulators, cyclothiazide, aniracetam and CX614, bind at overlapping binding sites in the dimer interface between two iGluR2 subunits. However, pharmacological data indicate that there are one or more additional binding sites for this class of compounds. Based on differences in structure-activity relationship data we show that 5-alkyl-benzothiadiazide (5ABTD) modulators and a series of close analogs of cyclothiazide, despite having a common core structure, do not have the same binding site. In the present work, a new potential binding site for allosteric modulators has been identified in the dimer interface of the iGluR2 ligand-binding domain. By comparing different iGluR2 crystal structures including different co-crystallized agonists, this cavity is shown to be a structurally conserved part of the dimer interface. The cavity is characterized with respect to shape and potential favorable interactions with ligands and docking is used to find a reasonable binding mode for the core structure of the 5ABTDs. The extensive structure-activity data available for this series of compounds are in agreement with the proposed binding mode, supporting the conclusion that the identified cavity most likely is the binding site for the 5ABTDs.     

Simulation of operational behaviour of patchily regenerated, rigid gas cleaning filter media

Particle removal from hot process gases is frequently accomplished with regenerable ceramic filters. When regenerating such media periodically, the dust cake may be detached from parts of the filter surface while other regions remain intact (‘patchy cleaning’). The filtration process depends on how these patterns of incomplete regeneration evolve over a number of cycles, how they change the build-up of the new cake, and how they affect the pressure drop. A two-dimensional quasi stationary flow model is used to predict pressure drops as a function of regeneration efficiencies and regeneration patterns, taking into account the finite thickness and flow resistance of the medium itself. The effect of non-uniform cake build-up on the pressure rise during a filter cycle is also modelled for a partially regenerated filter. The calculations prove that the pressure drop rises faster for lower regeneration efficiencies and that also cycle times become briefer with lower regeneration efficiency. It can also be shown, that the regeneration pattern only influences the pressure drop curve at the very beginning of the filtration cycle but does not influence the filtration cycle times.     

Ethanol flame structure investigated by molecular beam mass spectrometry

The oxidation of ethanol was studied in low-pressure, premixed flat flames using molecular beam mass spectrometry (MBMS) in combination with electron impact ionization (EI) and resonance-enhanced multiphoton ionization (REMPI). Flame temperature profiles were measured by laser-induced fluorescence (LIF) of seeded NO. Two ethanol/oxygen/argon flames with stoichiometries of ?=1.00 and ?=2.57 were investigated at 50 mbar by EI-MBMS. Profiles of a variety of stable and radical species were measured as a function of height above the burner. The benzene profile in the fuel-rich ethanol flame was obtained by REMPI-MBMS. The same technique was used to determine the dependence of the benzene concentration on the ethanol/propene ratio in low-pressure flames with blended fuels (propene/ethanol/oxygen/argon). The C/O ratio of all blends was kept constant at C/O=0.773 or C/O=0.600. Ethanol addition ranged from 0 to 15% for flames with C/O=0.773, and from 0 to 100% for flames with C/O=0.600. In both data sets, a decrease of the benzene concentration with increasing ethanol percentage was observed. Qualitative information on some other aromatic species with higher mass was also obtained.     

Diamond deposition and plasma diagnostics in a 27 MHz inductive coupled reactor (ICP)

An inductive coupled planar radio frequency (rf) reactor (ICP) with separately mounted concentric coils was used to deposit diamond films onto silicon and boron nitride. A grounded Faraday polarizer was mounted on top of the reactor below the rf-coil to prevent capacitive coupling. The electrically heated substrates were immersed in the most intense plasma region shaped like a torus. Mainly two different argon-hydrogen-methane mixtures were used, namely Ar/H₂/CH₄—250/25/0.5 sccm (mixture #I) and Ar/H₂/CH₄—50/50/0.5 sccm (mixture #II). With the conditions of mixture #I, deposition of good quality diamond with relatively high growth rates (0.6–1 μm h⁻¹) has been obtained. During diamond growth, the plasma was investigated by means of a Langmuir probe system (LP), providing radial distributions of several plasma parameters. The energy distributions of the most often occurring ions were analysed by an energy and mass spectrometer (EMS). Correlations between the measured parameters and the grown coatings will be given.